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PRESCRIBING INFORMATION
Pr
Cloxacillin for Injection
Cloxacillin Powder for Solution (as cloxacillin sodium)
500mg powder/vial
1g powder/vial
2g powder/vial
10g powder/vial
STERILE
Antibiotic
SteriMax Inc.
Date of Revision:
1-2735 Matheson Blvd. E.
January 24, 2013
Mississauga, ON
L4W 4M8
Control number: 156275
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TABLE OF CONTENTS
PART 1: HEALTH PROFESSIONAL INFORMATION………………………......
SUMMARY PRODUCT INFORMATION……………………………………...
INDICATIONS AND CLINICAL USE…………………………………………
CONTRAINDICATIONS……………………………………………………….
WARNINGS AND PRECAUTIONS……………………………………………
ADVERSE REACTIONS………………………………………………………..
DRUG INTERACTIONS………………………………………………………...
DOSAGE AND ADMINISTRATION…………………………………………..
OVERDOSAGE………………………………………………………………….
ACTIONS AND CLINCAL PHARMACOLOGY………………………………
STORAGE AND STABILITY…………………………………………………...
DOSAGE FORMS, COMPOSITION AND PACKAGING……………………..
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PART II: SCIENTIFIC INFORMATION...................................................................
PHARMACEUTICAL INFORMATION………………….............…….............
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PART III: CONSUMER INFORMATION.................................................................. 10
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PRESCRIBING INFORMATION
Pr
Cloxacillin for Injection
Cloxacillin Powder for Solution (as cloxacillin sodium)
PART I: HEALTH PROFESSIONAL INFORMATION
SUMMARY PRODUCT INFORMATION
Route of
Administration
Dosage Form /
Strength
IV, IM, IV Infusion
Powder for
reconstitution for
injection
Clinically Relevant Non-medicinal
Ingredients
None
INDICATIONS AND CLINICAL USE
The treatment of beta-hemolytic streptococcal and pneumococcal infections as well as
staphylococcal infections (including those caused by beta-lactamase producing
organisms). In severe staphylococcal infections (septicaemia, osteomyelitis, endocarditis,
pneumonia) or when staphylococci are suspected and treatment is required before
sensitivity results are available, parenteral cloxacillin should be administered at once,
followed by cloxacillin orally, when indicated.
It is not effective against the so called “methicillin-resistant” strains of staphylococcus.
If the results of identification and susceptibility testing indicate that the infection is due to
an organism other than a penicillinase producing staphylococcus susceptible to
cloxacillin sodium, treatment should be discontinued and therapy with an alternative
agent instituted.
CONTRAINDICATIONS
Cloxacillin for Injection is contraindicated for use:
•
in patients who are hypersensitive to this drug, to penicillin, or to cephalosporins
or to any component of the container. For a complete listing, see the Dosage
Forms, Composition and Packaging section of the Prescribing Information.
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WARNINGS AND PRECAUTIONS
Hematologic:
During long-term therapy, renal, hepatic and hematopoietic functions should be checked
periodically.
Hepatic:
During long-term therapy, renal, hepatic and hematopoietic functions should be checked
periodically.
Immune:
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been
reported in patients receiving penicillin or cephalosporin therapy. These reactions are
more apt to occur in individuals with a history or sensitivity to multiple allergens. Careful
inquiry should be made concerning previous hypersensitivity to reactions to penicillins,
cephalosporins or other allergens. If allergic or anaphylactic reactions occurs, discontinue
treatment and administer the usual agents, e.g. antihistamines, pressor amines,
corticosteroids. See Contraindications.
Neurologic:
The passage of any penicillin from blood into brain is facilitated by inflamed meninges
and during cardiopulmonary bypass. In the presence of such factors, particularly in renal
failure when high serum concentration can be attained, CNS adverse effects including
myoclonia, convulsive seizures and depressed consciousness can be expected. Although
this complication has not been reported with cloxacillin, it should be anticipated.
Sensitivity/Resistance:
Candidiasis and other superinfections may occur, especially in debilitated and
malnourished patients, or those with low resistance to infection due to corticosteroids,
immunosuppressors or irradiation. If superinfection occurs, institute appropriate
measures.
Renal:
During long-term therapy, renal, hepatic and hematopoietic functions should be checked
periodically.
Special Populations
Pregnant Women:
Safety in pregnancy has not yet been established.
Paediatrics:
Experience in premature and newborn infants is limited. Cautious administration of the
drug to such patients and frequent evaluation of organ system function is recommended.
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ADVERSE REACTIONS
Adverse Drug Reaction Overview
It may be expected the most common untoward reactions will be related to sensitivity.
They are more likely to occur in individuals who have previously demonstrated
hypersensitivity to penicillins and cephalosporins and in those with a history of allergy,
asthma, hay fever or urticaria. All degrees of hypersensitivity, including fatal
anaphylaxis, have been reported with penicillin.
Gastrointestinal:
Nausea, vomiting, epigastric discomfort, flatulence and loose stools have been noted in
some patients.
Hematologic: Eosinophilia, leucopenia, anemia, thrombocytopenia, thrombocytopenic,
purpura, neutropenia and agranulocytosis have been reported during therapy with
penicillins. These reactions are usually reversible on discontinuation of therapy and are
believed to be hypersensitivity phenomena. Thrombophlebitis has occurred during the
course of i.v. therapy. Mildly elevated SGOT level (less than 100 units) have been
reported.
Immune:
Allergic reactions (rash, urticaria) including wheezing and sneezing have been reported.
DRUG INTERACTIONS
Drug-Drug Interactions
Probenecid
As with other penicillins, concurrent administration of probenecid enhances the serum
concentration of cloxacillin.
DOSAGE AND ADMINISTRATION
Dosing Considerations:
Preparation and Storage of Parenteral Solution:
Tap vial gently to loosen powder. Use only Sterile Water for injection. Immediate use of
reconstituted solutions is recommended, however reconstituted solutions may be stored
for up to 24 hours at controlled room temperature not exceeding 25°C or 48 hours under
refrigeration. Products should be reconstituted as directed below and may be added to an
appropriate infusion fluid in the amount calculated to give the desired dose.
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For IM use: Using Sterile Water for Injection, reconstitute as follows:
Fill
Size
(mg)
250
500
Volume of
Diluent Added
(mL)
1.9
1.7
Withdrawable
Volume
(mL)
2.0
2.0
Nominal
Concentration
(mg/mL)
125
250
For IV Use: Using Sterile Water for Injection, reconstitute as follows:
Fill
Size
(mg)
250
500
1000
Volume of
Diluent
Added
(mL)
4.9
4.8
9.6
Withdrawable Nominal
Volume
Concentration
(mL)
5.0
5.0
10.0
(mg/mL)
50
100
100
For IV Infusion: Using Sterile Water for Injection, reconstitute as follows:
Fill
Size
(mg)
1000
2000
10000
Volume of
Diluent
Added
(mL)
3.4
6.8
34.0
Withdrawable Nominal
Volume
Concentration
(mL)
4.0
8.0
40.0
(mg/mL)
250
250
250
Cloxacillin for Injection should be reconstituted as described above and added to an
appropriate infusion fluid in the amount calculated to give the desired dose.
Recommended Dose and Dosage Adjustment:
Adults: 250 to 500 mg i.m. or i.v. every 6 hours. I.V. dosage may be increased in serious
infections. Maximum dosage for adults is 6 g/day.
Children (up to 20 kg): 25 to 50 mg/kg/day into 4 equal doses administered i.m. or i.v.
every 6 hours.
Administration:
IM/IV use: Shake well to dissolve. Administer total contents of vial by slow infusion
over 2-4 minutes. Immediate use of the reconstituted solution is recommended.
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IV Infusion: Shake well to dissolve. Administer total contents of vial by slow infusion
over 30-40 minutes. Immediate use of the reconstituted solution is recommended.
Dispensing from Pharmacy Bulk Vial: The use of pharmacy bulk vial is restricted to
hospitals with a recognized intravenous admixture program. The pharmacy bulk vial is
intended for single puncture, multiple dispensing.
OVERDOSAGE
For management of a suspected drug overdose, contact your regional
Poison Control Center immediately.
Treatment is likely needed only in patients with severely impaired renal function, since
patients with normal kidneys excrete penicillins at a fast rate. No specific treatment can
be recommended.
In patients with severe allergic reactions, general supportive measures (if the patient is in
shock) or symptomatic therapy similar to that applied in all cases of hypersensitivity are
recommended.
ACTION AND CLINICAL PHARMACOLOGY
Cloxacillin exerts a bacterial action against susceptible microorganisms during the stage
of active multiplication. It acts through the inhibition of biosynthesis of cell wall
mucopeptides.
Cloxacillin demonstrates activity against strains of beta-hemolytic streptococci,
pneumococci, penicillin G sensitive staphylococci and, due to its resistance to
penicillinase, penicillin G resistant (β-lactamase producing) staphylococci. Cloxacillin
displays less intrinsic antibacterial activity and a narrower spectrum than penicillin G.
Pharmacokinetics
Cloxacillin is stable in an acid medium and is approximately 50% absorbed orally. After
an oral dose of 500mg cloxacillin, a peak serum level of about 8 micrograms/mL is
reached in about 1 hour. The serum level after i.m. cloxacillin is approximately twice
that obtained when the same dose is given orally to fasting adults. Food in the stomach
or small intestine reduces absorption and peak serum levels are approximately 50% those
obtained after fasting. As with other penicillins, concurrent administration of probenecid
enhances the serum concentration.
Once absorbed, approximately 94% are bound to plasma proteins. After oral
administration, roughly 20% of the dose is excreted in the urine, together with one or
more active metabolites as yet unidentified. The half life of elimination is about 30
minutes.
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STORAGE AND STABILITY
Store dry powder at controlled room temperature 15-30°C.
Cloxacillin for Injection is compatible at concentrations of 1 and 2 mg/mL up to 12 hours
at controlled room temperature not exceeding 25°C in dextrose 5% in water, fructose
10% in water or normal saline, M/6 sodium lactate, Lactated Ringer’s invert sugar 10%
in water or normal saline.
Reconstituted solution may be stored for up to 24 hours at controlled room temperature
not exceeding 25°C or in refrigerator at 2°- 8°C (36° - 46°F) for up to 48 hours. Discard
unused portion.
DOSAGE FORMS, COMPOSITION AND PACKAGING
How Supplied:
Pr
Cloxacillin for Injection is supplied as a dry powder in vials containing: 500 mg, 1,000
mg, 2,000 mg, or 10 g of cloxacillin base as the sodium salt.
Each gram of Cloxacillin Sodium for injection contains approximately 50 mg, or
approximately 5-7% sodium.
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PART II: SCIENTIFIC INFORMATION
PHARMACEUTICAL INFORMATION
Drug Substance
Proper Name:
Chemical Name:
Cloxacillin sodium
6-[[[3-(2-Chlorophenyl)-5-methyl-4isoxazolyl[carbonyl]amino]3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2carboxylic acid, sodium salt
Empirical Formula:
Molecular Weight:
Structural Formula:
C19H17CIN3NaO5S • H2O
475.88
Physical Characteristics: Cloxacillin sodium is a white, crystalline powder
Solubility:
Soluble at 20°C in 2.5 parts water, in 30 parts ethanol (95%) and in
500 parts chloroform.
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IMPORTANT: PLEASE READ
PART III: CONSUMER INFORMATION
WARNINGS AND PRECAUTIONS
Pr
Cloxacillin for Injection
Cloxacillin Powder for Solution (as cloxacillin sodium)
BEFORE you use Cloxacillin for Injection talk to your doctor
or pharmacist if you have:
This leaflet is Part III of a three-part "Package insert"
published when Cloxacillin for Injection was approved for sale
in Canada and is designed specifically for Consumers.
•
•
•
•
•
•
This leaflet is a summary and will not tell you everything about
Cloxacillin for Injection. Contact your doctor or pharmacist if
you have any questions about the drug.
ABOUT THIS MEDICATION
kidney problems
liver problems
had allergic reactions before
been taking corticosteroid medication
been taking immunosuppressant medication
or are pregnant or planning a pregnancy
INTERACTIONS WITH THIS MEDICATION
What the medication is used for:
Drugs that may interact with Cloxacillin for Injection include:
Cloxacillin for Injection is used to treat streptococcus, pneumonia,
and staphylococcus bacterial infections.
•
Probenecid
Talk to your doctor or pharmacist about any other herbs or
vitamin supplements you may be taking.
What it does:
Cloxacillin prevents bacteria from reproducing, which allows your
body to fight only the existing bacteria. Cloxacillin for Injection is
given intravenously, intramuscularly, or through intravenous
infusion.
PROPER USE OF THIS MEDICATION
Usual Dose:
Adults: 200-500mg every 6 hours.
When it should not be used:
Children (up to 20kg): 25 to 50 mg/kg/day into 4 equal doses
every 6 hours.
Do not use Cloxacillin for Injection if:
•
This dose may be adjusted by your doctor depending on your
particular condition and age.
You are allergic to cloxacillin, penicillin, or
cephalosporin medication.
Overdose:
Contact a physician or your Local Poison control center
immediately for the management of an overdose even if there are
no symptoms.
What the medicinal ingredient is:
The medicinal ingredient in Cloxacillin for Injection is cloxacillin,
presented as cloxacillin sodium.
Missed Dose:
Consult your doctor if you miss a dose.
What the important nonmedicinal ingredients are:
There are no non-medicinal ingredients. As cloxacillin is
presented in its salt form, there are approximately 50mg of sodium
per 1g of active ingredient.
SIDE EFFECTS AND WHAT TO DO ABOUT THEM
Cloxacillin for Injection may cause some side effects such as
nausea, vomiting, gastrointestinal discomfort, gas, and diarrhea.
What dosage forms it comes in:
Cloxacillin for Injection is available in vials of 500mg, 1g, 2g, and
10 g of cloxacillin as cloxacillin sodium.
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IMPORTANT: PLEASE READ
SERIOUS SIDE EFFECTS, HOW OFTEN THEY
HAPPEN AND WHAT TO DO ABOUT THEM
Symptom / effect
Talk with your
doctor or
pharmacist
Only if
severe
Rare
In all
cases
Allergic reaction
(including skin
redness, rash,
sneezing, swelling
and trouble
breathing)
Weakness, weight
loss, general
malaise (due to
problems with
white or red blood
cells)
MORE INFORMATION
This document plus the full Prescribing Information, prepared for
health professionals can be obtained by contacting the sponsor,
SteriMax Inc. at: 1-800-881-3550.
Stop taking
drug and
seek
immediate
emergency
medical
attention
This leaflet was prepared by SteriMax Inc.
Last revised: January 14, 2013


This is not a complete list of side effects. For any unexpected
effects while taking Cloxacillin for Injection contact your doctor
or pharmacist.
REPORTING SUSPECTED SIDE EFFECTS
You can report any suspected adverse reactions associated with
the use of health products to the Canada Vigilance Program by
one of the following 3 ways:
-------------------------------------------------------------------------•
Report online at www.healthcanada.gc.ca/medeffect
•
Call toll-free at 1-866-234-2345
•
Complete a Canada Vigilance Reporting Form and:
- Fax toll-free to 1-866-678-6789, or
- Mail to: Canada Vigilance Program
Health Canada
Postal Locator 0701E
Ottawa, Ontario
K1A 0K9
Postage paid labels, Canada Vigilance Reporting Form
and the adverse reaction reporting guidelines are
available on the MedEffect™ Canada Web site at
www.healthcanada.gc.ca/medeffect.
NOTE: Should you require information related to the management
of side effects, contact your health professional. The Canada
Vigilance Program does not provide medical advice.
HOW TO STORE IT
Store Cloxacillin for Injection at controlled room temperature (15°
- 30°C).
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